Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8 and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population

  1. Ying Wu1,
  2. Huaixing Li1,
  3. Ruth J.F. Loos2,
  4. Zhijie Yu1,
  5. Xingwang Ye1,
  6. Lihua Chen1,
  7. An Pan1,
  8. Frank B. Hu (frank.hu{at}channing.harvard.edu)3 and
  9. Xu Lin (xlin{at}sibs.ac.cn)1
  1. 1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China
  2. 2MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Box 285, Hills Road, Cambridge, CB2 0QQ, UK
  3. 3Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA

    Abstract

    OBJECTIVE— Genome-wide association studies have identified common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX/IDE, EXT2 and LOC387761 loci that significantly increase risk of type 2 diabetes. We aimed to replicate these observations in a population-based cohort of Chinese Hans and examine the associations of these variants with type 2 diabetes and diabetes-related phenotypes.

    RESEARCH DESIGN AND METHODS— We genotyped 17 SNPs in 3,210 unrelated Chinese Hans, including 424 participants with type 2 diabetes, 878 with impaired fasting glucose (IFG) and 1,908 with normal fasting glucose (NFG).

    RESULTS— We confirmed the associations between type 2 diabetes and variants near CDKAL1 (OR 1.49 (1.27-1.75), P = 8.91×10-7) and CDKN2A/B (OR 1.31 [1.12-1.54], P = 1.0×10-3). We observed significant association of SNPs in IGF2BP2 (OR 1.17 [1.03-1.32], P = 0.014) and SLC30A8 (OR 1.12 [1.01-1.25], P = 0.033) with combined IFG/type 2 diabetes. The SNPs in CDKAL1, IGF2BP2 and SLC30A8 were also associated with impaired β-cell function estimated by HOMA-B. When combined, each additional risk allele from CDKAL1-rs9465871, CDKN2A/B-rs10811661, IGF2BP2-rs4402960 and SLC30A8-rs13266634 increased the risk for type 2 diabetes by 1.24 fold (P = 2.85×10-7) or for combined IFG/type 2 diabetes by 1.21 fold (P = 6.31×10-11). None of the SNPs in EXT2 or LOC387761 exhibited significant association with type 2 diabetes or IFG. Significant association was observed between the HHEX/IDE SNPs and type 2 diabetes in individuals from Shanghai only (P < 0.013), but not in those from Beijing (P > 0.33).

    CONCLUSIONS— Our results indicate that in Chinese Hans, common variants in CDKAL1, CDKN2A/B, IGF2BP2 and SLC30A8 loci independently or additively contribute to type 2 diabetes risk, likely mediated through β-cell dysfunction.

    Footnotes

      • Received January 14, 2008.
      • Accepted July 3, 2008.

    This Article

    1. Published online before print July 15, 2008, doi: 10.2337/db08-0047
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